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At least 19 recordsLinked to original sources

PubMed1978

Disopyramide: a review of its pharmacological properties and therapeutic use in treating cardiac arrhythmias.

Disopyramide is a new antiarrhythmic drug with a pharmacological profile of action similar to that of quinidine and procainamide. In a few controlled therapeutic trails and a large number of uncontrolled studies in patients with arrhythmias, often following a myocardial infarction, disopyramide has been relatively effective (more so in ventricular than in atrial arrhythmias) and usually well tolerated. In treating premature atrial and ventricular contractions, the best-studied area of its therapeutic use, disopyramide was superior to a placebo and of similar efficacy to but better tolerated than quinidine; the drop-out rate due to adverse effects of the disopyramide group (10%) being less than one-third that of the quinidine group (36%). In an open ward setting, disopyramide used prophylactically after myocardial infarction appeared to reduce both the incidence of reinfarction and the mortality rate, while in patients treated in coronary care units although the incidence of reinfarction was lower with disopyramide than with a placebo, the mortality rate was not significantly different. Further well-designed trials with adequate numbers of patients are needed before the routine use of disopyramide in infarct patients treated in either setting can be justified. Comparative studies are also required to determine if disopyramide has advantages over other antiarrhythmic agents in this area of use. Side-effects with disopyramide are usually a result of its anticholinergic activity, a dry mouth and difficulty in urination being the most common. Like other antiarrhythmic agents, disopyramide exerts a negative inotropic action on cardiac muscle, and development of acute heart failure has been reported. Development of worsening of heart block and hypotension have also occurred. Disopyramide is largely excreted unchanged and dosage should be reduced in patients with impaired renal function, in accordance with creatinine clearance values.

Arrhythmias, Cardiac↗

PubMed1977

Efficacy of disopyramide phosphate in the treatment of refractory ventricular tachycardia.

The effects of intravenously administered disopyramide phosphate were evaluated in seven patients with refractory ventricular tachycardia. All patients had organic heart disease, including acute infarction (three patients), chronic coronary artery disease (two patients) and cardiomyopathy (two patients). The severity of the heart disease was reflected in the advanced patient age (average 64 years) and the occurrence before disopyramide therapy of cardiac arrest in five patients and congestive heart failure in all seven patients. In five patients, disopyramide was given as a bolus injection, 2 mg/kg body weight, followed by an infusion of 20 to 40 mg/hour. The final two patients received 4 mg/kg divided as a bolus injection and an infusion over 1 hour followed by a 0.4 mg/kg infusion during the next hour. Intravenous administration of disopyramide resulted in more effective electrical stability in all patients and completely eliminated ventricular tachycardia in six. Recurrence of ventricular tachycardia was prevented in six patients with subsequent long-term oral administration of disopyramide. Possible dose-related cardiac pump depression occurred in two patients, but disopyramide was otherwise well tolerated. Therefore, these data document the therapeutic efficacy of disopyramide in the treatment of refractory life-threatening ventricular tachyarrhythmias.

Aged↗

PubMedDate not supplied

Disopyramide plasma and myocardial tissue concentrations as they relate to antiarrhythmic activity.

Antiarrhythmic concentrations of disopyramide in canine plasma and myocardium were determined by gas chromatography. Ventricular tachycardia was incuded in anesthetized dogs by the intravenous administration of ouabain. Disopyramide phosphate was then administered by a two-stage continuous infusion method. A rapid infusion of disopyramide (9.08 mg/kg/hr) was administered for 30 min, followed by a slow infusion (2.18 mg/kg/hr) to maintain steady-state plasma levels of 1.98-2.21, mean +/- SEM = 2.1 +/- 0.02 microgram/ml at the end of 2 hr. Myocardial tissue levels of disopyramide at steady-state plasma levels were four times those of plasma (atrial tissue, 8.91 +/- 0.10; right ventricular free wall, 8.93 +/- 0.13; left ventricular free wall, 9.11 +/- 0.16 microgram/gm wet tissue). The intravenous administration of 80 units crystalline zinc insulin produced both hypokalemia (3.78 +/- 0.22 reduced to 2.36 +/- 0.18 mEq potassium/liter plasma) and a reappearance of ventricular tachycardia despite no change in plasma and myocardial tissue concentrations of disopyramide from those which had been effective in establishing and maintaining sinus rhythm. The observations demonstrate a relationship between plasma and myocardial disopyramide concentrations such that the former can be used in assessing patient therapy. In addition, this study suggests the important of plasma potassium in determining the therapeutic effectiveness of disopyramide.

Animals↗

PubMedDate not supplied

The effects of urine pH and plasma protein binding on the renal clearance of disopyramide.

To ascertain whether the renal clearance of disopyramide (pKa = 8.36) is affected by urine pH, the disposition kinetics of disopyramide were compared during excretion of acidic and alkaline urine following both single dose intravenous (2mg/kg) and oral (5 mg/kg) administration to 4 healthy male volunteers. No significant difference was observed in the plasma concentration-time curve of disopyramide. The mean 72 hour recovery of disopyramide and its N-deisopropyl metabolite (MND) in urine was 55.1 and 20.3% of the dose respectively, with no apparent difference between the two routes of administration or pH of urine. Renal clearance of disopyramide was found to vary with time, which is partly the result of a concentration dependent change in plasma protein binding. The unbound fraction of drug in plasma varied from 0.32 to 0.72 between 0.4 to 4microgram/ml concentration. However, time-dependent change in renal clearance of disopyramide persists even after correction for plasma protein binding.

Administration, Oral↗

PubMed1978

Electrophysiology of disopyramide in man.

The electrophysiological effects of an intravenous dose of disopyramide phosphate (2 mg per kg body weight) were studied in 17 patients. Studies were performed with the patients fasting, unpremedicated, and off all medication for three days. Blood samples for estimation of serum levels of disopyramide were collected in 15 of these patients. The effects of intravenous disopyramide were maximal at five minutes, less marked at 20 minutes, and largely gone by 30 minutes after administration of the drug. Sinus cycle length and corrected sinus node recovery time were shortened significantly. No index of atrioventricular nodal function was significantly changed. Both atrial and ventricular effective refractory periods were significantly prolonged. Further impairment of intraventricular conduction occurred in six patients with bundle branch block on electrocardiogram or prolonged HV interval. In one of two patients with Wolff-Parkinson-White syndrome, the bypass effective refractory period was prolonged. These electrophysiological changes are similar to quinidine and quinidine like drugs. It is recommended that disopyramide should be used cautiously in patients with evidence of His Purkinje system disease since it may lead to higher degrees of intraventricular block.

Adolescent↗

PubMed1979

Intravenous disopyramide phosphate and ventricular overdrive pacing in the termination of paroxysmal ventricular tachycardia.

Both antiarrhythmic drugs and bursts of rapid ventricular pacing provide alternatives to DC cardioversion for the treatment of paroxysmal ventricular tachycardia. This report considers the individual and combined success of burst ventricular pacing and intravenous disopyramide phosphate in the tretment of 11 examples of paroxysmal ventricular tachycardia. Rapid ventricular pacing, at a rate of up to 50 beats/min faster than the tachycardia rate terminated 7 of the tachycardias. Intravenous disopyramide resulted in increased tachycardiac cycle length (342 +/- 34 ms-385 +/- 56 ms), increased QRS complex width (147 +/- 42 ms-180 +/- 41 ms) and termination of 8 the tachycardias. The remaining 3 tachycardias could be terminated by bursts of ventricular pacing following the infusion of disopyramide. Of these, 2 could not be terminated prior to disopyramide. The use of both techniques allowed the extinction of all 11 tachycardias and prevented the need to proceed to DC conversion.

Adult↗

PubMed1977

Effects of disopyramide and aprindine on arrhythmias after acute myocardial infarction.

The incidence of ventricular arrhythmias after myocardial infarction was compared in a double blind study of disopyramide (33 patients), aprindine (34 patients) and placebo (31 patients). Total ventricular arrhythmias were less frequent in the aprindine group than in the disopyramide group (P less than 0.05) or than in the combined disopyramide and placebo groups (P less than 0.05). The incidence of life-threatening arrhythmias and of ventricular arrhythmias in high risk patients was also reduced by aprindine compared to disopyramide (P less than 0.001) or placebo (P less than 0.001). It is concluded that aprindine is effective in reducing ventricular arrhythmias and that further investigations on its preventive use after the onset of myocardial infarction are justified.

Acute Disease↗

PubMed1976

[Antiarrhythmic effect of disopyramide in ventricular extrasystole and auricular fibrillation].

Disopyramide (B 712) was tested in 39 patients with chronic arrhythmias of different kind: 23 cases with atrial fibrillation, 16 cases with ventricular ectopic beats, two cases with supraventricular tachycardias. The effect of disopyramide was compared to a pretreatment with one or several antiarrhythmic drugs (quinidine, beta-blocking agents, verapamil, ajmalin-bitartrat, aprindine, propafenone, diphenylhydantoin) which had been discontinued either due to ineffectiveness or the occurrence of intolerable side effects. Therapeutical effectiveness was controlled by on-line arrhythmia computers in the CCU or Holter monitoring. 15 patients were treated longer than 4 weeks up to 16 months (mean 35+/-22,6 weeks). The following results were achieved: 1 atrial fibrillation, abolition or significant reduction of the rate of recurrence in 10 out of 23 patients; slight reduction or no effect in 13 patients; 2. ventricular ectopic beats: abolition or significant reduction in 6 out of 16 patients, slight reduction or no effect in the remaining 10 patients. Patients who were treated successfully received the same dosis as those without therapeutical success. In cases with atrial fibrillation, the success was dependent on the duration of this arrhythmia prior to treatment. In comparison to the pretreatment with one or several of the above-mentioned anti-arrhythmic drugs, disopyramide was as effective as the drug given before. The analysis of the Ecg revealed a slight but insignificant prolongation of the time intervals. In 22 patients reversible dosage-dependent side effects were observed which are due to the vagolytic action of the drug: dry mouth, blurred vision, urinary hesitancy, nausea, headache. These side effects occurred at daily dosages between 400 to 800 mg increasing markedly in patients on 800 mg a day. The drug had to be discontinued in 4 cases because of side effects. During long-term treatment no severe side effects were observed. Thus, disopyramide may serve as an alternative to quinidine, especially if the latter has to be stopped because of side effects.

Adolescent↗

PubMed1976

Oral disopyramide in prophylaxis of arrhythmias following myocardial infarction.

Oral disopyramide given prophylactically following myocardial infarction has been compared with placebo in a double-blind trial using continuous-tape monoriting of the electocardiogram. It caused a significant reduction in the incidence of ventricular arrhythmias and of the various degrees of heart-block. There was a significant reduction of reinfarction during hospital stay in patients who had received disopyramide. Disopyramide appears to be a safe and effective oral therapy in the prevention of potentially serious arrhythmias following myocardial infarction.

Administration, Oral↗

PubMed1977

Oral disopyramide for the prevention of arrhythmias in patients with acute myocardial infarction admitted to open wards.

Patients with acute myocardial infarction admitted to open wards of three hospitals were given either oral disopyramide (100 mg four times daily) or matching placebo, prophylactically, for seven days. The drug was associated with a significant reduction in mortality (p = 0-0025) and in incidence of extension of infarction (p = 0-01), ventricular fibrillation (p = 0-05), and ventricular tachycardia (p = 0-01). Disopyramide was not associated with any particular complication or side-effect. Unitl information is available to the contrary, oral disopyramide should be given for the first seven days after myocardial infarction to all patients not managed in an intensive-care unit.

Acute Disease↗

PubMedDate not supplied

Electrophysiological and hemodynamic disturbances in a patients overdosed with disopyramide.

Disopyramide exerts a quinidinelike effect on the heart and is a valuable drug for treating atrial and, especially, ventricular tachyarrhythmias. The therapeutic plasma concentration of disopyramide is thought to be 2.0-4.0 (5.0) microgram/ml. We here report the cardiac effects of a high dose of disopryamide in a patient with extensive coronary artery disease complicated by ventricular extrasystoles. At plasma levels above approximately 7.0 micrograms/ml, heart rate was decreased, while PQ interval, width, and QT interval were increased. At concentrations above approximately 6.0 micrograms/ml, disopyramide exerted negative intropic effects as judged by increases in mean right atrial, pulmonary arteriolar, and pulmonary capillary venous pressures and a decrease in cardiac output.

Adult↗

PubMedDate not supplied

Ventricular tachycardia-flutter associated with disopyramide therapy: a report of three cases.

Three patients developed episodes of ventricular tachycardia and/or flutter-fibrillation while receiving disopyramide (Norpace). Syncope was the presenting complaint in all of them. The arrhythmias did not recur after disopyramide was discontinued. The Q-T interval was markedly prolonged in all three patients. One patient developed syncope associated with both quinidine and Norpace therapy. It is postulated that disopyramide, like quinidine, may provoke ventricular flutter-fibrillation in sensitive patients by similar mechanisms.

Aged↗

PubMed1975

Effect of pKb on lipophilic binding of disopyramide derivatives to human plasma.

The extent of plasma binding, the partition coefficient, and the pKb of 13 disopyramide derivatives were determined. The structural variation on the diisopropylaminoethyl group of disopyramide molecules influenced these physical parameters to varying degrees. Results demonstrated that the extent of interaction between drugs and human plasma was a linear function of their lipophilicity and inversely proportional to the magnitude of the pKb value.

Blood Proteins↗

PubMed1975

Effects of disopyramide on electrophysiological properties of specialized conduction system in man and on accessory atrioventricular pathway in Wolff-Parkinson-White syndrome.

Seven patients with normal specialized conduction system and three patients with the Wolff-Parkinson-White (WPW) syndrome were studied using programmed stimulation of the heart before and after the administration of intravenous disopyramide. The principal effect of this drug was to prolong the effective refractory period of the atria and ventricles, and to prolong the effective refractory period of the anomalous pathway in the WPW syndrome. In addition, it prolonged the conduction time in the anomalous pathway in the WPW syndrome. These findings suggest that disopyramide would be a useful and safe drug in the management of certain atrial and ventricular arrhythmias and in the management of the Wolff-Parkinson-White syndrome with atrial fibrillation.

Adolescent↗

PubMed1979

Haemodynamic effects of disopyramide in patients after open-heart surgery.

Disopyramide phosphate was administered intravenously in a dose of 1.2 mg/kg body weight over one minute to nine patients after open-heart surgery and coronary artery bypass grafting. The haemodynamic changes were studied during and for 30 minutes after drug administration. Heart rate was unchanged throughout the study. During infusion the only significant changes were an increase in systemic blood pressure and systolic impedance signifying a direct increase in peripheral arterial resistance. Systemic blood pressure remained significantly higher for 10 minutes and systolic impedance for 30 minutes. Immediately after infusion max. dPower/dT, a measure of ventricular contractility, was significantly depressed for 15 minutes. Both cardiac output and aortic flow were significantly depressed for 30 minutes. DPTI/TTI, an estimate of subendocardial supply/demand ratio, showed an insignificant increase throughout the study. This study shows that intravenous disopyramide starts acting within 45 seconds of the start of infusion, directly increases peripheral arterial resistance, has a breif negative inotropic action, and does not reduce subendocardial blood flow.

Adult↗

PubMed1979

Disopyramide--an effective treatment for lignocaine resistant ventricular dysrhythmias.

Intravenous disopyramide was used in 13 patients who developed recurrent ventricular dysrhythmias despite initial treatment with intravenous lignocaine after admission to the Coronary Care Unit of a busy district hospital. This was effective in 8 of the 13 patients treated and there was no major side effects observed. Disopyramide has the advantage of being available both as an oral and an intravenous preparation and is a useful drug to be added to the list of more conventional anti-dysrhythmic agents.

Arrhythmias, Cardiac↗

PubMed1979

Liquid chromatographic analysis of disopyramide and its mono-N-dealkylated metabolite.

We describe a rapid, sensitive, and specific "high performance" liquid chromatographic analysis for disopyramide and its mono-N-dealkylated metabolite in serum, urine, and saliva. We used a mu-Bondapak CN column and an acetate buffer mobile phase containing methanol. Retention times for the two compounds and the internal standard, p-chlorodisopyramide, were 3.4, 4.1, and 6.3 min, respectively. The lower limits of sensitivity for drug and metabolite were 50 and 80 micrograms/L, respectively, with maximum coefficients of variation of 4.6 and 12%, respectively. Currently used antiarrhythmic drugs did not interfere with the analysis of disopyramide, and the pharmacokinetics of the drug, obtained from studies of one subject, agree well with reported values.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Pharmacokinetics and steady-state myocardial uptake of disopyramide in the dog.

The pharmacokinetics and steady-state myocardial uptake of the antiarrhythmic drug disopyramide (DP) were determined in dogs after oral or intravenous administration of [14C]disopyramide phosphate. DP was absorbed rapidly and its absolute oral bioavailability was about 70%. Significant dose-dependent kinetics were not apparent after 7.5- to 30-mg/kg po doses. Plasma half-lives of DP were about 2.9 and 1.2 hr after the po and iv doses, respectively. DP and its N-dealkylated metabolites were largely excreted in the urine and their composition was qualitatively similar after the po and iv doses. Marked differences in the protein binding of DP in human and dog plasma were found. In the papillary muscle, ventricular septum, and ventricles of one dog, the steady-state concentrations of DP and its less active mono-N-dealkylated metabolite were about twice those in plasma, whereas in the atria and tricuspid and mitral valves they were similar to those in plasma.

Administration, Oral↗